Inhibitors of amyloid beta-protein production
A method of protecting a warm-blooded mammal from the progression of Alzheimer's disease, which comprises administering an effective amount of a compound of general formula. ##STR1## in which: R.sup.1 represents an optionally substituted aromatic or heteroaromatic group;L.sup.1 and L.sup.2 each independently represents a bond or an unbranched (1-4C) alkylene group, which alkylene group may optionally bear a (1-4C) alkyl, phenyl or phenyl (1-2C) alkyl substituent;one of Y.sup.1 and Y.sup.2 represents NR.sup.3 and the other represents O, S or NR.sup.3, in which R.sup.3 represent hydrogen, hydroxyl, (1-4C) alkoxy, (1-4C) alkyl or di (1-4C) alkylamino;Z represents O or S; andR.sup.2 represents (3-8C) cycloalkyl, heterocyclyl, and optionally substituted aromatic or heteroaromatic group, or together with L.sup.2, (1-10C) alkyl;or a pharmaceutically acceptable salt thereof.
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Claims
1. A method of inhibiting the production of A.beta. peptide in a biological system, which comprises administering an effective amount of a compound of general formula ##STR7## in which Z is O or S;
- R.sup.11 is a halogen atom;
- R.sup.12 is a halogen atom or a trifluoromethyl group; and
- R.sup.7 is hydrogen, (1-8C)alkyl, (1-8C)haloalkyl, (1-8C) alkylthio, (1-8C)alkoxy or halogen;
- or a pharmaceutically acceptable salt thereof.
2. A method as claimed in claim 1, in which Z is O, R.sup.11 is a fluorine or chlorine atom, and R.sup.12 is a chlorine atoms or a trifluoromethyl group.
3. A method as claimed in claim 2 in which R.sup.7 is hydrogen, methyl, t-butyl, trifluoromethyl, 2chloro-2-methylpropyl, hexylthio, bromo or chloro.
5. A method of inhibiting the accumulation of A.beta. peptide in senile plaques in a warm-blooded mammal, which comprises administering an effective amount of a compound of general formula. ##STR8## in which Z is O or S;
- R.sup.11 is a halogen atom;
- R.sup.12 is a halogen atom or a trifluoromethyl group; and
- R.sup.7 is hydrogen, (1-8C)alkyl, (1-8C)haloalkyl, (1-8C)alkylthio, (1-8C)alkoxy or halogen;
- or a pharmaceutically acceptable salt thereof.
6. A method of protecting a warm-blooded mammal from the progression of Alzheimer's disease by inhibiting the formation of A.beta. peptide, which comprises administering an effective amount of a compound of general formula. ##STR9## in which Z is O or S;
- R.sup.11 is a halogen atom;
- R.sup.12 is a halogen atom or a trifluoromethyl group; and
- R.sup.7 is hydrogen, (1-8C)alkyl, (1-8C)haloalkyl, (1-8C) alkylthio, (1-8C)alkoxy or halogen;
- or a pharmaceutically acceptable salt thereof.
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Type: Grant
Filed: Mar 2, 1995
Date of Patent: Sep 29, 1998
Assignee: Eli Lilly and Company (Indianapolis, IN)
Inventors: Lawrence J. Heinz (Pittsboro, IN), Jill A. Panetta (Zionsville, IN), Michael L. Phillips (Indianapolis, IN), Jon K. Reel (Carmel, IN), John K. Shadle (Fishers, IN), Richard L. Simon (Greenwood, IN), Celia A. Whitesitt (Greenwood, IN)
Primary Examiner: Alan L. Rotman
Assistant Examiner: D. Margaret M. Mach
Attorneys: Arleen Palmberg, David E. Boone
Application Number: 8/398,188
International Classification: A61K 31415; A61K 31425; C07D285135;
